Kugita et al., U.S. Pat. No. 3,562,257 (Feb. 9, 1971), describes benzothiazepine derivatives, which are useful as antidepressants, tranquilizers and coronary vasodilators. Among these, diltiazem, i.e., 3-(acetyloxy)-5-[2-dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1, 5-benzothiazepin-4(5H)-one, is a well-known successful cardiac drug having calcium blocking activity. Vasodilating action is specific for the d-cis-isomer. The hydrochloride is often administered as, e.g., Cardizem.RTM..
As might be expected, various processes or methods for preparing such a benzothiazepine as diltiazem and its salts are generally further known. To permit isolation of the desired optically active isomer many of such methods include at least one resolution step.
Sanada et al., Jpn. Discl. No. 268663-1988 (Nov. 28, 1986), discloses (2R, 3S)-2,3-epoxy-3-(4-lower alkoxyphenyl)-propionic acid (-)-menthyl ester which is permitted to react with 2-aminothiophenol to produce 2(S)-hydroxy-3(S)-(4-lower alkoxyphenyl)-3-(2-aminophenylthio)propionic acid (-)-menthyl ester. Purportedly after hydrolysis, the acid product may be used to prepare corresponding 1,5-benzothiazepine derivatives, e.g., diltiazem hydrochloride.